Introduction
Stroke is one of the global leading causes of death and may cause long-term disability for many stroke survivors (Mendis, 2013; Andrew et al., 2014). Up to three-quarters of patients with poststroke experienced ongoing cognitive impairment (Pasi et al., 2012; Jokinen et al., 2015; Renjen et al., 2015). Cognitive impairment and functional disability are often associated with the following stroke. Furthermore, the depressive mode worsens the difficulties for patients with stroke to maintain their social and personal relationships. Clinical depression is characterized by behavioral, cognitive, and emotional features (Merriman et al., 2019). Cognitive performance is always associated with symptoms of depression (Nakling et al., 2017), and early cognitive deficits in patients after stroke may predict long-term depressive symptoms (Nys et al., 2006). Furthermore, poststroke cognitive impairment is associated with early and enduring activity limitations and participation restrictions (Stolwyk et al., 2021). These disorders might lead to a poor quality of life (QoL) for individuals with stroke and their families.
In recent years, interventions for poststroke motor and cognitive impairment, depression, and reduced functional independence have become the focus of international stroke rehabilitation research, and novel clinical rehabilitation therapies [e.g., virtual reality (VR), repetitive transcranial magnetic stimulation (rTMS), and robotic assistive therapies] have shown great potential in future practice (Langhorne et al., 2011; Winstein et al., 2016a; Gittler and Davis, 2018). VR-based training is defined by using computer hardware and software-generated user-computer interface for users to interact with virtual environments that relate to the real world to facilitate task-oriented training and provide multimodal feedback to augment functional recovery (Laver et al., 2017; Hao et al., 2021). Basic neuroscience behind VR-based treatment was the finding of mirror neurons (MNs) in the primary motor cortex (M1), dorsal premotor cortex, supplementary motor area (SMA), and M1 from animal studies (Gentilucci et al., 1988; Rizzolatti et al., 1996; Rizzolatti and Sinigaglia, 2016; Mekbib et al., 2020). The evidence from human neuroimaging suggested that the neural mechanisms of VR on neural plasticity and motor reorganization in humans might be to stimulate the internal sensorimotor system through activating MNs in the cortical and subcortical motor control-related areas, particularly M1, SMA, and cerebellum (August et al., 2006(Prochnow et al., 2013; Mekbib et al., 2020, 2021; Hao et al., 2021).
Recently, many clinical studies favored VR-based intervention for motor function, balance, gait, and activities of daily living (ADL) in patients with stroke. Although multiple systematic reviews and meta-analyses have indicated that VR-based training was useful for upper limb motor function, lower limb motor function, balance, gait, and activities of daily living (ADL) in stroke (Henderson et al., 2007; Laver et al., 2011; Saposnik et al., 2011; Lohse et al., 2014; Laver et al., 2015; de Rooij et al., 2016; Li et al., 2016; Silver, 2016; Yates et al., 2016; Laver et al., 2017; Aminov et al., 2018; Al-Whaibi et al., 2021; Fang et al., 2021; Peng et al., 2021; Zhang et al., 2021), two recent articles published in The Lancet Neurology by Saposnik et al. (2016) and Silver (2016) argued that the methodological issues that existed in some of the studies (Broeren et al., 2008; Kwon et al., 2012) were the comparison of VR combined with conventional rehabilitation vs. conventional rehabilitation alone without active control. Such study design (Saposnik et al., 2011; Lohse et al., 2014; Laver et al., 2015) might create an imbalance in the total rehabilitation time, and the effect might be induced by any active intervention and might not be explained by VR (Saposnik et al., 2016; Silver, 2016).
Conventional paper-and-pencil exercises and computer-assisted cognitive training designed to improve specific domains of cognitive deficits are widely used for patients with stroke with cognitive impairment. However, traditional cognitive training is limited by its insufficient personalization and adaptation and suboptimal intensity (Faria et al., 2016; Maier et al., 2020). Preliminary results (Kim et al., 2011; Choi et al., 2014; Faria et al., 2016, 2020; De Luca et al., 2018; Kannan et al., 2019; Maggio et al., 2019; Oh et al., 2019; Maier et al., 2020; Manuli et al., 2020) suggested that VR-based training combined with traditional rehabilitation might be more effective for enhancing cognition, depressive mood, and QoL in stroke than traditional cognitive rehabilitation. However, there is no clear evidence concerning the effectiveness of VR for cognition, depression, and QoL in patients with stroke (Laver et al., 2011, 2015; Silver, 2016). Recently, several systematic reviews (Aminov et al., 2018; Wiley et al., 2020; Zhang et al., 2021) have evaluated the effectiveness of VR for cognitive impairment in patients with stroke. Aminov et al. (2018) included 4 studies that assess VR-based rehabilitation on cognitive outcomes and found that VR could induce significant gains on improvements in cognitive function. Zhang et al. (2021) combined 7 RCTs to evaluate the effectiveness of VR interventions for cognitive outcomes compared with control groups, but no significant difference was found. However, in the two meta-analyses (Aminov et al., 2018; Zhang et al., 2021), only global cognition examined by MMSE or MoCA test for screening cognitive impairment was included, and specific domains of cognition were not investigated. Wiley et al. (2020) performed a systematic review that included five manuscripts to evaluate VR-based intervention combined with rehabilitation exercise on global cognition and specific domains of cognition and concluded that VR therapy was not better than traditional rehabilitation interventions for enhancing cognitive function in stroke survivors. However, due to the limited number of original articles, small sample size, different types of VR devices, different VR intervention durations, and different stages after stroke onset, the results remain controversial.
To date, however, few systematic reviews and meta-analyses have investigated VR-based training for cognitive function in contrast to cognitive exercise or motor exercise on the chronic stage of stroke. Therefore, this study aimed to explore the effect of VR-based training on cognition, motor function, mood, and ADL among individuals at the chronic phase of stroke.[…]
TBI Rehabilitation 